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Hydrochloric Acid → [1-(2-{5-[6-(4-{2-[4-Cyano-1-(2-methoxycarbonylamino-2-phenyl-acetyl)-pyrrolidin-2-yl]-3H-imidazol-4-yl}-phenyl)-naphthalen-2-yl]-1H-imidazol-2-yl}-4-methylene-pyrrolidine-1-carbonyl)-2-methyl-propyl]-carbamic acid methyl ester

HRID 1751417
Notizen
Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 1751417
C(O[C:6]([N:8]1[CH2:12][CH:11]([C:13]#[N:14])[CH2:10][CH:9]1[C:15]1[NH:16][C:17]([C:20]2[CH:25]=[CH:24][C:23]([C:26]3[CH:35]=[CH:34][C:33]4[C:28](=[CH:29][CH:30]=[C:31]([C:36]5[NH:37][C:38]([CH:41]6[CH2:45][C:44](=[CH2:46])[CH2:43][N:42]6[C:47](=[O:57])[CH:48]([NH:52][C:53]([O:55][CH3:56])=[O:54])[CH:49]([CH3:51])[CH3:50])=[N:39][CH:40]=5)[CH:32]=4)[CH:27]=3)=[CH:22][CH:21]=2)=[CH:18][N:19]=1)=[O:7])(C)(C)C.Cl.[CH3:59][O:60][C:61]([NH:63][CH:64]([C:68]1[CH:73]=[CH:72][CH:71]=[CH:70][CH:69]=1)C(O)=O)=[O:62].CCN(C(C)C)C(C)C.CCOC(C(C#N)=NOC(N1CCOCC1)=[N+](C)C)=O.F[P-](F)(F)(F)(F)F>C(Cl)Cl.O1CCOCC1>[CH3:56][O:55][C:53](=[O:54])[NH:52][CH:48]([C:47]([N:42]1[CH2:43][C:44](=[CH2:46])[CH2:45][CH:41]1[C:38]1[NH:37][C:36]([C:31]2[CH:30]=[CH:29][C:28]3[C:33](=[CH:34][CH:35]=[C:26]([C:23]4[CH:22]=[CH:21][C:20]([C:17]5[NH:16][C:15]([CH:9]6[CH2:10][CH:11]([C:13]#[N:14])[CH2:12][N:8]6[C:6](=[O:7])[CH:64]([NH:63][C:61]([O:60][CH3:59])=[O:62])[C:68]6[CH:73]=[CH:72][CH:71]=[CH:70][CH:69]=6)=[N:19][CH:18]=5)=[CH:25][CH:24]=4)[CH:27]=3)[CH:32]=2)=[CH:40][N:39]=1)=[O:57])[CH:49]([CH3:51])[CH3:50]
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Komponenten

8

Edukt 5

HCID 313Hydrochloric AcidHCID 81531DiisopropylethylamineHCID 596264N-Methoxycarbonyl-2-phenylglycineHCID 75951468(1-Cyano-2-ethoxy-2-oxoethylidenaminooxy)dimethylamino-morpholino-carbenium hexafluorophosphateHCID 773353874-Cyano-2-{5-[4-(6-{2-[1-(2-methoxycarbonylamino-3-methyl-butyryl)-4-methylene-pyrrolidin-2-yl]-3H-imidazol-4-yl}-naphthalen-2-yl)-phenyl]-1H-imidazol-2-yl}-pyrrolidine-1-carboxylic acid tert-butyl ester

Produkt 1

HCID 77335245[1-(2-{5-[6-(4-{2-[4-Cyano-1-(2-methoxycarbonylamino-2-phenyl-acetyl)-pyrrolidin-2-yl]-3H-imidazol-4-yl}-phenyl)-naphthalen-2-yl]-1H-imidazol-2-yl}-4-methylene-pyrrolidine-1-carbonyl)-2-methyl-propyl]-carbamic acid methyl ester

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6344DichloromethaneLösungsmittelHCID 312751,4-DioxaneLösungsmittel

Versuchsvorschrift

4-Cyano-2-{5-[4-(6-{2-[1-(2-methoxycarbonylamino-3-methyl-butyryl)-4-methylene-pyrrolidin-2-yl]-3H-imidazol-4-yl}-naphthalen-2-yl)-phenyl]-1H-imidazol-2-yl}-pyrrolidine-1-carboxylic acid tert-butyl ester (102.0 mg, 0.134 mmol) was stirred in DCM (2.0 mL)/HCl in dioxane (4M, 2.0 mL). After 40 minutes all volatiles were removed in vacuo. The crude material was dissolved in DMF (1.5 mL) and methoxycarbonylamino-phenyl-acetic acid (28.2 mg, 0.134 mmol), DIEA (52.2 mg, 0.4 mmol), and COMU (57.7 mg, 0.134 mmol) was added and stirring at room temperature was continued. After 15 minutes, the reaction was quenched with aqueous HCl (1N, 0.1 mL). The crude reaction mixture was purified via RP-HPLC (eluent: water/MeCN w/0.1% TFA). The product containing fractions were lyophilized to give the final compound (59.3.0 mg).

Aufarbeitung

  1. customAfter 40 minutes all volatiles were removed in vacuo
  2. dissolutionThe crude material was dissolved in DMF (1.5 mL)
  3. customthe reaction was quenched with aqueous HCl (1N, 0.1 mL)
  4. customThe crude reaction mixture
  5. customwas purified via RP-HPLC (eluent: water/MeCN w/0.1% TFA)
  6. additionThe product containing fractions

Quellen und Nachweise

ORD-Eintrag
ord-2d8fb952f32f44fb9056caaf090a92aa
Quelldatensatz
uspto-grants-2015_10
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US09156823B2

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